磷脂酰肌醇-3激酶的表达及其活性变化与妊娠期糖尿病胰岛素抵抗的关系
Relationship between variation of phosphatidyl inositol-3 kinase expression and activity and insulin resistance in pregnant women with gestational diabetes mellitus
摘要目的 研究磷脂酰肌醇-3激酶(phosphatidyl inositol-3 kinase,PI-3K)在妊娠期糖尿病(gestational diabetes mellitus,GDM)患者脂肪组织中的表达及其活性变化,分析其与GDM胰岛素抵抗(insulin resistance,IR)的关系.方法 采用Western印迹法、RT-PCR法分别检测20例GDM孕妇(GDM组)和20例正常妊娠晚期孕妇(正常妊娠组)脂肪组织中PI-3K p85α蛋白质和mRNA的表达,采用ELISA法检测两组孕妇脂肪组织中PI-3K的活性,葡萄糖氧化酶法和放射免疫法检测两组孕妇空腹血糖(fasting plasma glucose,FPG)及空腹胰岛素(fasting insulin,FIN)水平,并采用稳态模型(homeostasis model assessment,HOMA)计算IR指数.结果 (1)PI-3K p85a蛋白的表达GDM组高于正常妊娠组(0.93±0.04和0.71±0.06,P<0.01).(2)GDM组PI-3K p85emRNA表达高于正常妊娠组(0.83±0.03和0.53±0.07,P<0.01).(3)GDM组PI-3K的活性为正常妊娠组的30%,明显降低(1.7±0.6和5.2±0.5,P<0.01)(4)GDM组FPG、FINS、HOMA-IR分别为(5.8±0.2)mmol/L、(14.8±0.2)mmol/L和1.3±0.4,正常晚孕组分别为(4.7±0.3)mmol/L、(11.2±0.3)mmol/L和0.9±0.3,两组间各指标比较均有统计学意义(P<0.01).PI-3K活性与HOMA-IR呈负相关(r=-0.68,P<0.01).结论 GDM患者脂肪组织中PI-3K活性降低是其发生胰岛素抵抗的分子机制之一.
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abstractsObjective To investigate the variations of the expression and activity of phosphatidyl inositol-3 kinase(PI-3K)in the adipose tissue of pregnant women with gestational diabetes mellitus(GDM)and to explore its relationship with insulin resistance(IR)in these women.Methods The expression of PI-3K p85aprotein and mRNA in adipose tissue were detected by Western blot and Semi quantitative reverse transcription polymerase chain reaction(RT-PCR)in 20 GDM women(GDM group)and 20 normal pregnant women(normal group).The activity of PI-3K was determined by ELISA and IR index was calculated using homeostasis model assessment(HOMA)according to the results of fasting insulin(FINS)and fasting plasma glucose(FPG),which measured by oxidase assay and immunoradioassay,respectively.Results The expressions of PI-3K p85αmRNA and PI-3K p85a protein were markedly increased in the adipose tissue of GDM group than in the normal group(mRNA:0.83±0.03 vs 0.53±0.07,P<0.01;protein:0.93±0.04 vs 0.71±0.06,P<0.01).However,the PI-3K activity in the GDM groups was significantly down-regulated compared with the normal group(1.7±0.6 vs 5.2±0.5,P<0.01).The levels of FPG and FINS (HOMA-IR)in the GDM group were all significantly higher than the normal group[FPG:(5.8±0.2)mmol/L vs(4.7±0.3)mmol/L;FINS:(14.8±0.2)mmol/L vs(11.2±0.3)mmol/L;HOMA-IR:1.3±0.4 vs 0.9±0.3,a11 P<0.01]. Conclusions The decreased activity of PI-3K in the adipose tissue may be one of the molecular mechanisms for IR in GDM.
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